The broad purpose of the research proposed herein is to specifically regulate the immune response to one given molecule, in particular one that serves as a transplantation antigen. These studies will be performed largely with congenic resistant and recombinant strains of mice that differ from each other only with respect to the H-2D region of the major histocompatibility complex. Our immunosuppressive reagents will be antisera produced against H-2 antigen specific helper factors. We have already produced a heteroantiserum (rat-anti-mouse) against the supernatants containing antigen specific helper factor and are presently attempting to raise monoclonal antibodies that will be directed only aginst the antigen specific helper activity itself. We also propose to produce mouse-anti-mouse heoper factor sera with allotype congenic mice and with H-2 congenic mice. These antisera may have specificity for constant region versus idiotype regions of the helper molecule, respectively. Our preliminary data with rabbit antisera directed against nonspecific supernatants derived from murine 2-step MLR, (H-2 differences) suggest that skin graft survival can be significantly prolonged following a single 0.25 ml injection of these antisera at the time of skin grafting. Significant prolongation of graft survival is evident when the donor-recipient pairs differ for H-2 antigens but not when they differ for H-Y or non-MHC antigens. Besides antigen specific immunoregulation/immunosuppression, we will utilize this system to gain a greater understanding of 1) antigen specific helper factor molecules; 2) the relationship of such helper molecules to the antigen specific helper T cell receptor for antigen; 3) the isolation and characterization of cells capable of binding (absorbing) the antigen specific helper factors.